Role of the GTPase Rab22a during antigen cross presentation by dendritic cells

CEBRIAN, I; MAYORGA, LS

Rosario

Congreso; SAIB 50º; 2014

SAIB

Cross presentation is the process by which exogenous antigens are processed and presented to the class I molecules of histocompatibility complex (MHC) to activate a CD8+ T cell response. Dendritic cells (DCs) have been shown to be the most adapted antigen presenting cells to perform efficiently cross presentation. To do this, DCs have developed a strong specialization of their internalization pathway and many of the intracellular features used for cross presentation have been elucidated. Nevertheless several open questions remain unclear, for instance to determine how the peptides derived from exogenous antigens are loaded into MHC-I molecules. We consider that recycling compartments may have an important role in this step of cross presentation by modulating the trafficking of MHC-I molecules. So, we focus our study on Rab22a, a GTPase that participates in the recycling of MHC-I molecules. We found that this protein localized to recycling compartments in DCs and was recruited to phagosomes very early after latex beads internalization. After silencing the expression of Rab22a, DCs failed to cross present antigens efficiently and this defect could not be explained by a lack of MHC-I molecules expression. These results evidence a critical role for Rab22a in antigen cross presentation and point it out as a potential target for immunotherapy.